UK drugmaker AstraZeneca has suffered a major setback in a pivotal phase 3 trial to expand the indication for its rare heart disease treatment "Wainua." The market also raised criticism that there were problems with the trial design.
AstraZeneca said on the 9th (local time) that Wainua, co-developed with Ionis, failed to meet the primary endpoint in a global phase 3 trial in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
Wainua is currently sold in about 20 countries as a treatment for hereditary ATTR polyneuropathy (ATTR-PN).
ATTR is a rare disease in which transthyretin (TTR) protein accumulates in organs; when it affects the peripheral nerves, it is classified as hereditary ATTR polyneuropathy (ATTR-PN), and when it affects the heart, it is classified as ATTR cardiomyopathy (ATTR-CM). AstraZeneca conducted this trial to expand the indication to ATTR-CM, which has more patients. Last year, Wainua's sales were $212 million.
On the news of the trial failure, AstraZeneca's share price fell nearly 10% intraday, and its market capitalization at one point decreased by about £23.3 billion (about 4.72 trillion won). In contrast, shares of U.S. biotech companies Alnylam and BridgeBio, which have competing ATTR cardiomyopathy treatments, rose on expectations of a windfall.
The trial enrolled 1,432 patients across 20 countries. Over 140 weeks, Wainua was evaluated on whether it reduced cardiovascular death and recurrent cardiovascular events, but it failed to demonstrate a statistically significant improvement over placebo. However, in the patient group not using existing stabilizers, the monotherapy showed "nominal significance" in improving the composite endpoint.
The market raised not only the trial results but also criticism of the trial design itself.
In this trial, 57% of patients were already taking stabilizers at the start, and 24% received additional stabilizers during the trial. With existing therapies used concurrently, analysts said it was difficult to clearly prove Wainua's effect.
Bank of America (BofA) said, "Considering the trial results for rival Alnylam's Amvuttra, this failure was an outcome investors did not anticipate."
Jefferies said, "AstraZeneca has been highly regarded for its strong clinical trial design capabilities, and this failure could somewhat dent management's credibility." It added, however, that "the impact on the company's 2030 sales target and long-term growth is limited."
The setback follows negative developments in May, when AstraZeneca faced design-related criticism during the U.S. Food and Drug Administration (FDA) review of its breast cancer therapy "camizestrant."
Meanwhile, Barclays projected that AstraZeneca is unlikely to launch a new trial focused solely on Wainua monotherapy. Even if a new trial begins, it would take considerable time to secure approval, and it would be difficult to close the gap with Alnylam, which has already established a lead in the market.